Neoadjuvant chemo-radiotherapy for locally advanced esophageal cancer: a monocentric study

Tumori. 2012 Jul-Aug;98(4):451-7. doi: 10.1177/030089161209800409.

Abstract

Aims and background: Multimodal therapy is a keystone of care in advanced esophageal cancer. Although neoadjuvant chemoradiotherapy is known to provide a survival advantage in selected cases, reliable prognostic and response predictive factors remain elusive. We report the outcome in a series of esophageal cancer patients treated at our center and the results of a retrospective analysis of epidermal growth factor receptor (EGFR) expression and EGFR/HER2 gene copy numbers taken as possible prognostic and predictive factors.

Methods and study design: Between 2001 and 2009, a total of 40 consecutive patients (34 men and 6 women; median age, 59 years) were treated for esophageal cancer.

Treatment: cisplatin, 80 mg/m² day 1, and 5-fluorouracil, 800 mg/m²/24 h on days 1-5, every 21 days, concomitant with 3D-conformal radiotherapy (54-59.4 in 30-33 fractions) for three up to four cycles. Surgery was performed in eligible patients 6-8 weeks after chemoradiation. EGFR expression and EGFR/HER2 amplification and gene copy number were studied by immunohistochemical analysis and fluorescence in situ hybridization, respectively.

Results: Acceptable toxicity following chemoradiation was recorded, with G3-G4 hematological toxicity in 20% of patients and G3-G4 dysphagia in less than 10%; 14 (35%) patients achieved complete response and 19 (48%) partial response; 18 underwent surgery after chemoradiation, of which 8 (20%) achieved pathologic complete response. The median survival was 29 months (95% CI, 25.7-32.1): 42 months for the resected and 20 for the unresected patients. EGFR and HER2 analysis in 28 patients showed that 89% had immunohistochemical EGFR expression, with 5 cases of EGFR and 10 of HER2 gene gain without a significant difference in response rate and survival in these patient subgroups.

Conclusions: Our results suggest a better outcome in patients who underwent surgery after chemoradiation. A larger sample size is necessary to clarify the role of EGFR and HER2 gene gain in predict response and survival.

MeSH terms

  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Alcohol Drinking / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Dose Fractionation, Radiation
  • Drug Administration Schedule
  • ErbB Receptors / analysis
  • ErbB Receptors / genetics*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / etiology
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / radiotherapy
  • Esophageal Neoplasms / surgery
  • Esophageal Neoplasms / therapy*
  • Esophagectomy*
  • Female
  • Fluorouracil / administration & dosage
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Imaging, Three-Dimensional
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Neoplasm Staging
  • Radiotherapy, Adjuvant
  • Radiotherapy, Conformal* / adverse effects
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics*
  • Retrospective Studies
  • Risk Factors
  • Smoking / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Cisplatin
  • Fluorouracil